临床试验/NCT01915498

NCT01915498已完成1 期

A Phase 1/2, Multicenter, Open-Label, Dose-Escalation and Expansion, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Orally Administered AG-221 in Subjects With Advanced Hematologic Malignancies With an IDH2 Mutation

Celgene24 个研究点分布在 2 个国家目标入组 345 人开始时间: 2013年8月27日最近更新: 2024年10月22日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Celgene
入组人数: 345
试验地点: 24
主要终点: Phase 1 Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLT)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The primary objectives of Phase 1 Dose Escalation/Part 1 Expansion are:

To assess the safety and tolerability of treatment with enasidenib administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle in participants with advanced hematologic malignancies.
To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and/or the recommended Phase 2 dose (RP2D) of enasidenib in participants with advanced hematologic malignancies.

The primary objective of Phase 2 is:

• To assess the efficacy of enasidenib as treatment for participants with relapsed or refractory (R/R) acute myelogenous leukemia (AML) with an IDH2 mutation.

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Sequential
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Subject must be greater than or equal to 18 years of age.
•Subjects must have an advanced hematologic malignancy including:
•Phase 1/ Dose escalation:
•Diagnosis of acute myelogenous leukemia (AML) according to World Health Organization (WHO) criteria;
•Disease refractory or relapsed (defined as the reappearance of > 5% blasts in the bone marrow).
•Untreated AML, greater than or equal to 60 years of age and are not candidates for standard therapy due to age, performance status, and/or adverse risk factors, according to the treating physician and with approval of the Medical Monitor;
•Diagnosis of Myelodysplastic syndrome (MDS) according to WHO classification with refractory anemia with excess blasts (RAEB-1 or RAEB-2), or considered high-risk by the Revised International Prognostic Scoring System (IPSS-R), that is recurrent or refractory, or the subject is intolerant to established therapy known to provide clinical benefit for their condition (i.e., subjects must not be candidates for regimens known to provide clinical benefit), according to the treating physician and with approval of the Medical Monitor.
•Phase 1/Part 1 Expansion:
•Arm 1: Relapsed or refractory AML and age greater than or equal to 60 years or any subject with AML regardless of age who has relapsed following a bone marrow transplant (BMT).
•Arm 2: Relapsed or refractory AML and age <60 years, excluding subjects with AML who have relapsed following a BMT.
•Arm 3: Untreated AML and age greater than or equal to 60 years that decline standard of care chemotherapy.
•Arm 4: Isocitrate dehydrogenase protein, 2 (IDH2)-mutated advanced hematologic malignancies not eligible for Arms 1 to
•Diagnosis of AML according to World Health Organization (WHO) criteria and disease relapsed or refractory as defined by:
•Subjects who relapse after allogeneic transplantation;
•Subjects in second or later relapse;
•Subjects who are refractory to initial induction or re-induction treatment
•Subjects who relapse within 1 year of initial treatment, excluding patients with favorable-risk status according to National Comprehensive Cancer Network (NCCN) Guidelines. Favorable-risk cytogenetics: inv(16), t(16;16), t(8;21), t(15;17)
•Subjects must have documented IDH2 gene-mutated disease:
•For subjects in the dose escalation phase and Part 1 Expansion, IDH2 mutation may be based on local evaluation. (Centralized testing will be performed retrospectively.)
•For subjects in the Phase 2 portion of the trial, central testing of IDH2 mutation of bone marrow aspirate and peripheral blood, is required during screening to confirm eligibility
•Subjects must be amenable to serial bone marrow sampling, peripheral blood sampling and urine sampling during the study.
•The diagnosis and evaluation of AML or MDS will be made by bone marrow aspiration and/or biopsy. If an aspirate is unobtainable (i.e., a "dry tap"), the diagnosis may be made from the core biopsy.
•Screening bone marrow aspirate and peripheral blood samples are required of all subjects. A bone marrow biopsy must be collected if adequate aspirate is not attainable unless:
•A bone marrow aspirate and biopsy was performed as part of the standard of care within 28 days prior to the start of the study treatment; and
•Slides of bone marrow aspirate, biopsy and stained peripheral blood smear are available for both local and central pathology reviewers; and
•A bone marrow aspirate sample acquired within 28 days prior to the start of study treatment has been sent for cytogenetic analysis.
•Subjects must be able to understand and willing to sign an informed consent. A legally authorized representative may consent on behalf of a subject who is otherwise unable to provide informed consent, if acceptable to and approved by the site and/or sites Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
•Subjects must have Eastern Cooperative Oncology Group (ECOG) Performance status (PS) of 0 to
•Platelet count ≥ 20,000/μL (transfusions to achieve this level are allowed). Subjects with a baseline platelet count of < 20,000/μL due to underlying malignancy are eligible with Medical Monitor approval.
•Subjects must have adequate hepatic function as evidenced by:
•Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN), unless considered due to Gilbert's disease, a gene mutation in UGT1A1, or leukemic organ involvement, following approval by the Medical Monitor;
•Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) ≤ 3.0 × ULN, unless considered due to leukemic organ involvement.
•Subjects must have adequate renal function as evidenced by:
•Serum creatinine ≤ 2.0 × ULN OR
•Creatinine clearance greater than 40 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR) estimation: (140 - Age) x (weight in kg) x (0.85 if female)/72 x serum creatinine
•Subjects must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer. (Subjects with residual Grade 1 toxicity, for example Grade 1 peripheral neuropathy or residual alopecia, are allowed with approval of the Medical Monitor)
•Female subjects of child-bearing potential must agree to undergo medically supervised pregnancy test prior to starting study drug. The first pregnancy test will be performed at screening (within 7 days prior to first study drug administration), and on the day of the first study drug administration and confirmed negative prior to dosing and Day 1 before dosing all subsequent cycles.
•Female subjects with reproductive potential must have a negative serum pregnancy test within 7 days prior to the start of therapy. Subjects with reproductive potential are defined as sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy or tubal occlusion or who have not been naturally postmenopausal (i.e., who have not menstruated at all) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). Females of reproductive potential as well as fertile men and their partners who are female of reproductive potential must agree to abstain from sexual intercourse or to use two highly effective forms of contraception from the time of giving informed consent, during the study and for 120 days (females and males) following the last dose of AG-
•A highly effective form of contraception is defined as hormonal oral contraceptives, injectables, patches, intrauterine devices, double-barrier method (e.g., synthetic condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), or male partner sterilization.
•Able to adhere to the study visit schedule (ie, clinic visits at the study sites are mandatory, unless noted otherwise for particular study visits) and other protocol requirements.

排除标准

•Subjects who have undergone hematopoietic stem cell transplant (HSCT) within 60 days of the first dose of AG-221, or subjects on immunosuppressive therapy post HSCT at the time of screening, or with clinically significant graft-versus-host disease (GVHD). (The use of a stable dose of oral steroids post GVHD and/or topical steroids for ongoing skin GVHD is permitted with Medical Monitor approval.)
•Subjects who received systemic anticancer therapy or radiotherapy < 14 days prior to their first day of study drug administration. (Hydroxyurea is allowed for up to 28 days after the start of AG-221 for the control of peripheral leukemic blasts in subjects with white blood cell [WBC] counts > 30,000/μL as well as prior to enrollment).
•Subjects who received a small molecule investigational agent < 14 days prior to their first day of study drug administration. In addition, the first dose of AG-221 should not occur before a period ≥ 5 half-lives of the investigational agent has elapsed.
•Subjects taking the following sensitive cytochrome P450 (CYP) substrate medications that have a narrow therapeutic range are excluded from the study unless they can be transferred to other medications within ≥5 half-lives prior to dosing: paclitaxel (CYP2C8) warfarin, phenytoin (CYP2C9), S-mephenytoin (CYP2C19), thioridazine (CYP2D6), theophylline and tizanidine (CYP1A2).
•Subjects taking the P-glycoprotein (P-gp) and breast cancer resistant protein (BCRP) transporter-sensitive substrates digoxin and rosuvastatin should be excluded from the study unless they can be transferred to other medications within ≥ 5 half-lives prior to dosing.
•Subjects for whom potentially curative anticancer therapy is available.
•Subjects who are pregnant or lactating.
•Subjects with an active severe infection that required anti-infective therapy or with an unexplained fever > 38.5°C during screening visits or on their first day of study drug administration (at the discretion of the Investigator, subjects with tumor fever may be enrolled).
•Subjects with known hypersensitivity to any of the components of AG-
•Subjects with New York Heart Association (NYHA) Class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) < 40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan within approximately 28 days of Cycle 1, Day 1 (C1D1).
•Subjects with a history of myocardial infarction within the last 6 months of screening.
•Subjects with uncontrolled hypertension (systolic blood pressure [BP] >180 mmHg or diastolic BP > 100 mmHg) at screening are excluded. Subjects requiring 2 or more medications to control hypertension are eligible with Medical Monitor approval.
•Subjects with known unstable or uncontrolled angina pectoris.
•Subjects with a known history of severe and/or uncontrolled ventricular arrhythmias.
•Subjects with heart-rate corrected QT (QTc) interval ≥ 450 msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) at screening.
•Subjects taking medications that are known to prolong the QT interval unless they can be transferred to other medications within ≥ 5 half-lives prior to dosing.
•Subjects with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C.
•Subjects with any other medical or psychological condition, deemed by the Investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate, or participate in the study.
•Subjects with known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.
•Subjects with clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia.
•Subjects with immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.
•In the Phase 2 portion of the trial only, subjects who have previously received treatment with an inhibitor of Isocitrate dehydrogenase ( IDH).

研究组 & 干预措施

enasidenib

Experimental

enasidenib administered orally. Multiple doses will be administered to determine the RP2D.

干预措施: Enasidenib (Drug)

结局指标

主要结局

Phase 1 Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLT)

时间窗: From time of first dose up to the end of Cycle 1; 28 days

Toxicity severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. A DLT was defined as: • Non-hematologic toxicities: CTCAE ≥ Grade 3 with the exception of ≥ Grade 3 blood bilirubin increases in participants with a uridine diphosphate- glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) mutation. In participants with a UGT1A1 mutation, blood bilirubin increases of \> 5× upper limit of normal (ULN) were considered a DLT. • Hematologic toxicities: Prolonged myelosuppression, defined as persistence of ≥ Grade 3 neutropenia or thrombocytopenia (by NCI CTCAE v4.03), leukemia-specific criteria, i.e., marrow cellularity \<5% on Day 28 or later from the start of study drug without evidence of leukemia) at least 42 days after the initiation of Cycle 1 therapy. Leukemia-specific grading was used for cytopenias (based on percentage decrease from Baseline: 50 to 75% = Grade 3, \>75% = Grade 4)

Phase 1 Dose Escalation: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

时间窗: From the first dose of investigational product (IP) up to 28 days after the last dose, up to the data cutoff date of 01 September 2017; median treatment duration in the dose escalation phase was 5.0 months (range 0.4 to 34.2 months).

A TEAE is any adverse event that began or worsened on or after the start of investigational product (IP) through 28 days after the last dose. A treatment-related TEAE is a TEAE that is suspected (possibly or probably related) by the Investigator to be related to the IP. A serious AE is one that at any dose of IP or at any time during the observation period met the following criteria: • Resulted in death; • Was life threatening; • Requires inpatient hospitalization or prolongation of existing hospitalization; • Resulted in persistent or significant disability/incapacity; • Was a congenital anomaly/birth defect; • Was medically important. The intensity of each AE was graded from 1 to 5 according to the NCI CTCAE Version 4.03, and according to the following: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3), Life threatening (Grade 4), or Death (Grade 5).

Phase 1 Dose Expansion: Number of Participants With Treatment Emergent Adverse Events

时间窗: From the first dose of investigational product (IP) up to 28 days after the last dose of IP up to the data cutoff date of 01 September 2017; median treatment duration in Part 1 Expansion was 5.2 months (range 0.5 to 32.8 months).

A TEAE is any adverse event that began or worsened on or after the start of investigational product (IP) through 28 days after the last dose. A treatment-related TEAE is a TEAE that is suspected (possibly or probably related) by the Investigator to be related to the IP. A serious AE is one that at any dose of IP or at any time during the observation period met the following criteria: • Resulted in death; • Was life threatening; • Required inpatient hospitalization or prolongation of existing hospitalization; • Resulted in persistent or significant disability/incapacity; • Was a congenital anomaly/birth defect; • Was medically important. The intensity of each AE was graded from 1 to 5 according to the NCI CTCAE Version 4.03, and according to the following: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3), Life threatening (Grade 4), or Death (Grade 5).

Phase 2 Dose Expansion: Investigator Assessed Overall Response Rate (ORR)

时间窗: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).

ORR is defined as the percentage of participants achieving an overall response of complete response (CR), CR with incomplete neutrophil recovery (CRi), CR with incomplete platelet recovery (CRp), partial response (PR), or morphologic leukemia-free state (MLFS) based on the 2003 revised International Working Group (IWG) criteria for AML, assessed by the Investigator. CR: • Absolute neutrophil count (ANC) \> 1.0 x10⁹/L • Platelet count \> 100 x10⁹/L • Bone marrow (BM) blasts \< 5% • Absence of blasts with Auer rods • Independence of red cell transfusions CRi: • All CR criteria except for residual neutropenia (ANC \< 1.0 x 10⁹/L CRp: • All CR criteria except for residual thrombocytopenia (platelets \< 100 x 10⁹/L) PR: • Meets hematologic criteria of CR • Decrease of BM blasts to 5-25% and decrease of pretreatment BM blast ≥ 50%. MLFS: • Bone marrow blasts \< 5% • Absence of blasts with Auer rods • Absence of extramedullary disease • No hematologic recovery required

Phase 2 Dose Expansion: Number of Participants With Treatment Emergent Adverse Events

时间窗: From the first dose of investigational product (IP) up to 28 days after the last dose, up to the data cutoff of date of 01 September 2017; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).

A TEAE is any adverse event that began or worsened on or after the start of investigational product (IP) through 28 days after the last dose. A treatment-related TEAE is a TEAE that is suspected (possibly or probably related) by the Investigator to be related to the IP. A serious AE is one that at any dose of IP or at any time during the observation period met the following criteria: - Resulted in death; - Was life threatening; - Required inpatient hospitalization or prolongation of existing hospitalization; - Resulted in persistent or significant disability/incapacity; - Was a congenital anomaly/birth defect; - Was medically important. The intensity of each AE was graded from 1 to 5 according to the NCI CTCAE Version 4.03, and according to the following: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3), Life threatening (Grade 4), or Death (Grade 5).

Safety Follow-up: Number of Participants With Treatment Emergent Adverse Events

时间窗: From the primary analysis cut-off date of 01 September 2017 to the final analysis cut-off date of 29 July 2019, a maximum of 23 months.

A TEAE is any adverse event that began or worsened on or after the start of investigational product (IP) through 28 days after the last dose. A treatment-related TEAE is a TEAE that is suspected (possibly or probably related) by the Investigator to be related to the IP. A serious AE is one that at any dose of IP or at any time during the observation period met the following criteria: - Resulted in death; - Was life threatening; - Required inpatient hospitalization or prolongation of existing hospitalization; - Resulted in persistent or significant disability/incapacity; - Was a congenital anomaly/birth defect; - Was medically important. The intensity of each AE was graded from 1 to 5 according to the NCI CTCAE Version 4.03, and according to the following: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3), Life threatening (Grade 4), or Death (Grade 5).

次要结局

Phase 1 Dose Escalation: Investigator Assessed Overall Response Rate (ORR) by Total Daily Dose(Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in the dose escalation phase was 5.0 months (range 0.4 to 34.2 months).)
Phase 2: Maximum Concentration (Cmax) of Enasidenib After Single and Multiple Oral Doses(Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose.)
Phase 1 Dose Expansion: Investigator Assessed Overall Response Rate (ORR)(Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Expansion was 5.2 months (range 0.5 to 32.8 months).)
Combined Phase 1/2: Investigator Assessed Overall Response Rate in Participants With R/R AML(Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure for Phase 1 and 2 R/R AML participants was 5.4 months (range 0.4 to 34.2 months).)
Phase 1 Dose Escalation: Complete Response Rate (CRR) by Total Daily Dose(Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Escalation was 5.0 months (range 0.4 to 34.2 months).)
Phase 1 Dose Expansion: Complete Response Rate(Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Expansion was 5.2 months (range 0.5 to 32.8 months).)
Phase 2 Dose Expansion: Complete Response Rate(Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).)
Phase 1 Dose Escalation: Rate of Complete Response and Complete Response With Incomplete Hematological Recovery (CR/CRi/CRp) by Total Daily Dose(Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in the Phase 1 Dose Escalation was 5.0 months (range 0.4 to 34.2 months).)
Phase 1 Dose Expansion: Rate of Complete Response and Complete Responses With Incomplete Hematological Recovery (CR/CRi/CRp)(Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Expansion was 5.2 months (range 0.5 to 32.8 months).)
Phase 2 Dose Expansion: Rate of Complete Response and Complete Responses With Incomplete Hematological Recovery (CR/CRi/CRp)(Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).)
Phase 1 Dose Expansion: Kaplan-Meier Estimate of Duration of Response (DOR)(From first dose of study treatment to the data cut-off date of 01 September 2017; overall median time on follow-up in Phase 1 Dose Expansion was 8.3 months (range 0.5 to 32.8 months).)
Phase 2 Dose Expansion: Kaplan-Meier Estimate of Duration of Response(From first dose of study treatment to the data cut-off date of 01 September 2017; median time on follow-up in Phase 2 was 5.8 months (range 0.4 to 22.5 months).)
Phase 1 Dose Expansion: Kaplan-Meier Estimate of Overall Survival(From first dose of study treatment to the data cut-off date of 01 September 2017; overall median time on follow-up in Phase 1 Dose Expansion was 8.3 months (range 0.5 to 32.8 months).)
Phase 2 Dose Expansion: Kaplan-Meier Estimate of Overall Survival(From first dose of study treatment to the data cut-off date of 01 September 2017; median time on follow-up in Phase 2 was 5.8 months (range 0.4 to 22.5 months).)
Phase 1 Combined: Percentage of Participants Who Achieved 56-Day Red Blood Cell Transfusion Independence Post-baseline(Baseline to the end of treatment; overall median duration of treatment exposure in Phase 1 combined was 5.1 months (range 0.4, 34.2 months).)
Phase 1 Combined: Percentage of Participants Who Achieved 56-Day Platelet Transfusion Independence Post-baseline(Baseline to the end of treatment; overall median duration of treatment exposure in Phase 1 combined was 5.1 months (range 0.4, 34.2 months).)
Phase 2: Percentage of Participants Who Achieved 56-Day Red Blood Cell Transfusion Independence Post-baseline(Baseline to the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).)
Phase 2: Percentage of Participants Who Achieved 56-Day Platelet Transfusion Independence Post-baseline(Baseline to the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).)
Phase 1 Dose Expansion: Kaplan-Meier Estimate of Event Free Survival (EFS)(From first dose of study treatment to the data cut-off date of 01 September 2017; overall median time on follow-up in Phase 1 Dose Expansion was 8.3 months (range 0.5 to 32.8 months).)
Phase 2 Dose Expansion: Kaplan-Meier Estimate of Event Free Survival(From first dose of study treatment to the data cut-off date of 01 September 2017; median time on follow-up in Phase 2 was 5.8 months (range 0.4 to 22.5 months).)
Phase 1 Dose Expansion: Kaplan-Meier Estimate of Duration of Complete Response (DOCR)(From first dose of study treatment to the data cut-off date of 01 September 2017; overall median time on follow-up in Phase 1 Dose Expansion was 8.3 months (range 0.5 to 32.8 months).)
Phase 2 Dose Expansion: Duration of Complete Response(From first dose of study treatment to the data cut-off date of 01 September 2017; median time on follow-up in Phase 2 was 5.8 months (range 0.4 to 22.5 months).)
Phase 1 Dose Escalation: Time to First Response by Total Daily Dose(Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Escalation was 5.0 months (range 0.4 to 34.2 months).)
Phase 1 Dose Expansion: Time to First Response(Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Expansion was 5.2 months (range 0.5 to 32.8 months).)
Phase 2 Dose Expansion: Time to First Response(Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).)
Phase 1 Dose Escalation: Time to Best Response by Total Daily Dose(Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Escalation was 5.0 months (range 0.4 to 34.2 months).)
Phase 1 Dose Expansion: Time to Best Response(Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Part 1 Dose Expansion was 5.2 months (range 0.5 to 32.8 months).)
Phase 2 Dose Expansion: Time to Best Response(Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).)
Phase 1 Dose Escalation: Time to Complete Response by Total Daily Dose(Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in the Phase 1 Dose Escalation phase was 5.0 months (range 0.4 to 34.2 months).)
Phase 1 Dose Expansion: Time to Complete Response(Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Part 1 Dose Expansion was 5.2 months (range 0.5 to 32.8 months).)
Phase 2 Dose Expansion: Time to Complete Response(Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).)
Phase 1: Area Under the Plasma Concentration Time Curve From Time Zero to 8 Hours Postdose (AUC0-8) of Enasidenib After a Single Oral Dose on Day -3(Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose.)
Phase 1: Area Under the Plasma Concentration Time Curve From Time Zero to 10 Hours Postdose (AUC0-10) of Enasidenib After a Single Oral Dose on Day -3(Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose.)
Phase 1: Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of Enasidenib After a Single Oral Dose on Day -3(Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours post-dose.)
Phase 1: Area Under the Plasma Concentration Time Curve From Time Zero to 72 Hours Postdose (AUC0-72) of Enasidenib After a Single Oral Dose on Day -3(Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose.)
Phase 1: Area Under the Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Enasidenib After a Single Oral Dose on Day -3(Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose.)
Phase 1: Maximum Concentration of Enasidenib After a Single Oral Dose on Day -3(Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose.)
Phase 1: Time to Maximum Concentration (Tmax) of Enasidenib After a Single Oral Dose on Day -3(Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose.)
Phase 1: Apparent Terminal Phase Half-life (t½) of Enasidenib After a Single Oral Dose on Day -3(Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose.)
Phase 1: AUC From Time Zero to 8 Hours Postdose (AUC0-8) of Enasidenib After Multiple Oral Doses(Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose.)
Phase 1: AUC From Time Zero to 10 Hours Postdose (AUC0-10) of Enasidenib After Multiple Oral Doses(Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose.)
Phase 1: AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Enasidenib After Multiple Oral Doses(Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose.)
Phase 1: Maximum Concentration (Cmax) of Enasidenib After Multiple Oral Doses(Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose.)
Phase 1: Time to Maximum Concentration (Tmax) of Enasidenib After Multiple Oral Doses(Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose.)
Phase 2: Area Under the Plasma Concentration Time Curve From Time Zero to 8 Hours Postdose (AUC0-8) of Enasidenib After Single and Multiple Oral Doses(Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, and 8 hours post-dose.)
Phase 2: Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours Postdose (AUC 0-24) of Enasidenib After Single and Multiple Oral Doses(Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose.)
Phase 2: Apparent Terminal Phase Half-life (t1/2) of AGI-16903 After Single and Multiple Oral Doses of Enasidenib(Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose.)
Phase 2: Area Under the Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Enasidenib After Single and Multiple Oral Doses(Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose.)
Phase 2: Time to Maximum Concentration (Tmax) of Enasidenib After Single and Multiple Oral Doses(Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose.)
Phase 2: Apparent Terminal Phase Half-life (t1/2) of Enasidenib After Single and Multiple Oral Doses(Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose.)
Phase 1: AUC From Time Zero to 8 Hours Postdose (AUC0-8) of AGI-16903 After a Single Oral Dose of Enasidenib on Day -3(Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose.)
Phase 1: AUC From Time Zero to 10 Hours Postdose (AUC0-10) of AGI-16903 After a Single Oral Dose of Enasidenib on Day -3(Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose.)
Phase 1: AUC From Time Zero to 24 Hours Postdose (AUC0-24) of AGI-16903 After a Single Oral Dose of Enasidenib on Day -3(Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours post-dose.)
Phase 1: AUC From Time Zero to 72 Hours Postdose (AUC0-72) of AGI-16903 After a Single Oral Dose of Enasidenib on Day -3(Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose.)
Phase 1: AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t) of AGI-16903 After a Single Oral Dose of Enasidenib on Day -3(Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose.)
Phase 1: Maximum Concentration of AGI-16903 After a Single Oral Dose of Enasidenib on Day -3(Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose.)
Phase 1: Time to Maximum Concentration (Tmax) of AGI-16903 After a Single Oral Dose of Enasidenib on Day -3(Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose.)
Phase 1: Apparent Terminal Phase Half-life (t½) of AGI-16903 After a Single Oral Dose of Enasidenib on Day -3(Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose.)
Phase 1: AUC From Time Zero to 8 Hours Postdose (AUC0-8) of AGI-16903 After Multiple Oral Doses of Enasidenib(Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose.)
Phase 1: AUC From Time Zero to 10 Hours Postdose (AUC0-10) of AGI-16903 After Multiple Oral Doses of Enasidenib(Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose.)
Phase 1: AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t) of AGI-16903 After Multiple Oral Doses of Enasidenib(Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose.)
Phase 1: Maximum Concentration (Cmax) of AGI-16903 After Multiple Oral Doses of Enasidenib(Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose.)
Phase 1: Time to Maximum Concentration (Tmax) of AGI-16903 After Multiple Oral Doses of Enasidenib(Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose.)
Phase 2: AUC From Time Zero to 8 Hours Postdose (AUC0-8) of AGI-16903 After Single and Multiple Oral Doses of Enasidenib(Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, and 8 hours post-dose.)
Phase 2: AUC From Time Zero to 24 Hours Postdose (AUC0-24) of AGI-16903 After Single and Multiple Oral Doses of Enasidenib(Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose.)
Phase 2: AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t) of AGI-16903 After Single and Multiple Oral Doses of Enasidenib(Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose.)
Phase 2: Maximum Concentration (Cmax) of AGI-16903 After Single and Multiple Oral Doses of Enasidenib(Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose.)
Phase 2: Time to Maximum Concentration (Tmax) of AGI-16903 After Single and Multiple Oral Doses of Enasidenib(Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose.)
Phase 1 and 2: AUC From Time Zero to 8 Hours Postdose (AUC0-8) After Single and Multiple Oral Doses of Enasidenib 100 mg QD(Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, and 8 hours post-dose.)
Phase 1 and 2: AUC From Time Zero to 24 Hours Postdose (AUC0-24) After Single and Multiple Oral Doses of Enasidenib 100 mg QD(Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, 8, and 24 hours post-dose.)
Phase 1 and 2: Maximum Concentration (Cmax) After Single and Multiple Oral Doses of Enasidenib 100 mg QD(Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, 8, and 24 hours post-dose.)
Phase 1 and 2: Time to Maximum Concentration (Tmax) After Single and Multiple Oral Doses of Enasidenib 100 mg QD(Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, 8, and 24 hours post-dose.)
Phase 1 and 2: AUC From Time Zero to 8 Hours Postdose (AUC0-8) of AGI-16903 After Single and Multiple Oral Doses of Enasidenib 100 mg QD(Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, and 8 hours post-dose.)
Phase 1 and 2: AUC From Time Zero to 24 Hours Postdose (AUC0-24) of AGI-16903 After Single and Multiple Oral Doses of Enasidenib 100 mg QD(Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, 8, and 24 hours post-dose.)
Phase 1 and 2: Maximum Concentration (Cmax) of AGI-16903 After Single and Multiple Oral Doses of Enasidenib 100 mg QD(Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, 8, and 24 hours post-dose.)
Phase 1 and 2: Time to Maximum Concentration (Tmax) of AGI-16903 After Single and Multiple Oral Doses of Enasidenib 100 mg QD(Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, 8, and 24 hours post-dose.)
Phase 1: Percent Change From Baseline for Area Under the Effect Concentration Time Curve From Time 0 to 10 Hours Postdose (%BAUEC0-10) of 2-hydroxyglutarate (2-HG) on Day -3(Screening visit, Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose.)
Phase 1: Minimum Percent Change From Baseline Response Value Post-dose Over 10 Hours (%BRmin) for 2-HG After a Single Oral Dose of Enasidenib on Day -3(Screening visit, Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose.)
Phase 1: Time of Minimum Observed Concentration Over 72 Hours Postdose (Tmin) of 2-HG After a Single Oral Dose of Enasidenib on Day -3(Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose.)
Phase 1: Percent Change From Baseline for Area Under the Effect Concentration Time Curve From Time 0 to 10 Hours Postdose of 2-HG After Multiple Oral Doses of Enasidenib(Cycle 1, Day 15 and Cycle 2, Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose.)
Phase 1: Minimum Percent Change From Baseline Response Value Post-dose Over 10 Hours (%BRmin) for 2-HG After Multiple Oral Doses of Enasidenib(Cycle 1, Day 15 and Cycle 2, Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose.)
Phase 1: Time of Minimum Observed Concentration Over 10 Hours Postdose (Tmin) of 2-HG After Multiple Oral Doses of Enasidenib(Cycle 1, Day 15 and Cycle 2, Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose.)

研究者

发起方

Celgene

申办方类型

Industry

责任方

Sponsor

研究点 (24)

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